Molecular epidemiology of Plasmodium vivax and Plasmodium falciparum malaria among Duffy-positive and Duffy-negative populations in Ethiopia

Lo, Eugenia; Yewhalaw, Delenasaw; Zhong, Daibin; Zemene, Endalew; Degefa, Teshome; Tushune, Kora; Ha, Margaret; Lee, Ming‐Chieh; James, Anthony A.; Yan, Guiyun

doi:10.1186/s12936-015-0596-4

Cited by 60 publications

(93 citation statements)

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“…The P. vivax infections in Duffy-null Ethiopians is less severe than in Duffypositive Ethiopians (20) as was observed in Madagascar (14). From the Ethiopian sample collection, we identified two Duffynull individuals infected with P. vivax.…”

Section: Resultsmentioning

confidence: 87%

“…There are many other ligands that may explain the findings, including those yet to be described. P. vivax is not yet adapted to Duffy-null Africans in that it now causes a less severe infection than in Duffy-positive people (14,20). The concern is that P. vivax may adapt to infection in Duffy-blood-group-null Africans such that it may become a new cause of severe disease (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

“…Genomic DNA of each sample was amplified in duplicate for verification. In addition, parasite DNA content was estimated using the SYBR Green qPCR detection method using species-specific primers that targeted the 18S rRNA genes (20,49). All PCR assays included positive controls of both P. falciparum 7G8 (MR4-MRA-926) and HB3 (MR4-MRA-155) isolates as well as P. vivax Pakchong (MR4-MRA-342G) and Nicaragua (MR4-MRA-340G) isolates (MR4, https://www.beiresources.org/About/MR4.aspx, in addition to negative controls, including uninfected samples and water.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, Duffy-null individuals were found to be infected with P. vivax, both throughout Africa (Kenya, Madagascar, Mauritania, Cameroon, Angola, Equatorial Guinea, Ethiopia, and Sudan) and in South America (12)(13)(14)(15)(16)(17)(18)(19)(20)(21), raising the question: How can P. vivax invade in the absence of Duffy blood group expression? Is it possible that mutations in the cysteine-rich region 2 of the P. vivax DBP1 allows binding to another protein on the surface of Duffy-null erythrocytes, unrelated to the Duffy?…”

Section: Dna Expansionmentioning

confidence: 99%

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Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Gunalan

Hostetler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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121

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The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion.Plasmodium vivax | Duffy blood group antigen | Duffy-binding protein | DNA expansionI n 1975 we identified the failure of Plasmodium knowlesi to invade Duffy-null erythrocytes (1). We assumed that the Duffy blood group null phenotype, a common African phenotype, conferred resistance in Africans to P. vivax, a Plasmodium closely related to P. knowlesi. Subsequent studies demonstrated that African American volunteers who were Duffy-null were resistant to mosquito-transmitted P. vivax (2). In addition, African American soldiers in Vietnam who were infected with P. vivax were all Duffypositive (3). Furthermore, African Americans in a village in Honduras who were infected with P. vivax were all Duffy-positive whereas those infected with P. falciparum were both Duffy-null and -positive (4). We concluded that Duffy null was the basis of resistance to P. vivax by Africans.The molecular basis of Duffy null was a single point mutation in the GATA1-binding sequence in the promotor region 5′ to the Duffy blood group ORF (Fig. 1B) that led to Duffy-blood-groupnull erythrocytes (5). In vitro studies with P. knowlesi demonstrated that the invasive merozoites were able to bind and reorient apically with Duffy-null erythrocytes but could not form a junction as occurred in Duffy-positive erythrocytes, indicating that the Duffy blood group was required for P. vivax invasion (6). Later, in P. knowlesi parasite culture supernatants, the parasite ligand binding to Duffy blood group antigen was identi...

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Dna Expansionmentioning

confidence: 99%

See 2 more Smart Citations

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Gunalan

Hostetler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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121

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“…To date, this has been mainly accounted for by the absence of the red blood cell surface Duffy antigen among Africans living in this area [4]. Meanwhile, however, P. vivax infections were documented in Duffy-negative subjects in Brazil [5, 6], Ethiopia [7, 8], Madagascar [9], but also in West African countries, such as Mauritania [10], Cameroon [11, 12], Equatorial Guinea, and Angola [13]. According to these different studies, the prevalence of P. vivax in West-Africa is probably underestimated and large-scale epidemiological studies are thus required to investigate the burden of P. vivax infections [3].…”

Section: Introductionmentioning

confidence: 99%

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects

Poirier

Doderer-Lang

Atchade

et al. 2016

Malar J

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Background Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P. vivax in local populations. MethodsThe presence of P. vivax was investigated in a large population of healthy blood donors in Benin using microscopy, serology and molecular detection. The seroprevalence was measured with species-specific ELISA using two recombinant P. vivax proteins, namely rPvMSP1 and rPvCSP1. Specific molecular diagnosis of P. vivax infection was carried out using nested-PCR. The performances and cut-off values of both rPvCSP1 and rPvMSP1 ELISA were first assessed using sera from P. vivax-infected patients and from non-exposed subjects.ResultsAmong 1234 Beninese blood donors, no parasites were detected when using microscopy, whereas 28.7% (354/1234) of patients exhibited had antibodies against rPvMSP1, 21.6% (266/1234) against rPvCSP1, and 15.2% (187/1234) against both. Eighty-four samples were selected for nested-PCR analyses, of which 13 were positive for P. vivax nested-PCR and all Duffy negative. ConclusionThe results of the present study highlight an unexpectedly high exposure of Beninese subjects to P. vivax, resulting in sub-microscopic infections. This suggests a probably underestimated and insidious parasite presence in western Africa. While the vaccination campaigns and therapeutic efforts are all focused on Plasmodium falciparum, it is also essential to consider the epidemiological impact of P. vivax.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1620-z) contains supplementary material, which is available to authorized users.

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Human genetics and malaria resistance

2020

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Malaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells. They include the classical polymorphisms that cause sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. More recently however, with improving technology and experimental design, others have been identified that include the Dantu blood group variant, polymorphisms in the red cell membrane protein ATP2B4, and several variants related to the immune response. Characterising how these genes confer their effects could eventually inform novel therapeutic approaches to combat malaria. Nevertheless, all together, only a small proportion of the heritable component of malaria resistance can be explained by the variants described so far, underscoring its complex genetic architecture and the need for continued research.

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Molecular epidemiology of Plasmodium vivax and Plasmodium falciparum malaria among Duffy-positive and Duffy-negative populations in Ethiopia

Cited by 60 publications

References 43 publications

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects

Human genetics and malaria resistance

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